Efficacy, dose–response relationship and safety of once‐daily extended‐release metformin (Glucophage® XR) in type 2 diabetic patients with inadequate glycaemic control despite prior treatment with diet and exercise: results from two double‐blind, placebo‐controlled studies
Abstract
AIM: The efficacy, dose-response relationships and safety of an extended-release formulation of metformin (Glucophage) XR) were evaluated in two double-blind, randomized, placebo-controlled studies of 24 and 16 weeks' duration, in patients with inadequate glycaemic control despite diet and exercise. Protocol 1 provided an evaluation of metformin XR at a commonly used dosage. Protocol 2 evaluated different dosages of metformin XR. METHODS: In Protocol 1, 240 patients were randomized to receive metformin XR 1000 mg once daily. or placebo in a 2:1 ratio for 12 weeks (patients could receive metformin XR 1500 mg during weeks 12-24 if required). In Protocol 2, 742 patients were randomized to receive metformin XR 500 mg once daily, 1000 mg once daily, 1500 mg once daily, 2000 mg once daily, 1000 mg twice daily or placebo for 16 weeks. The primary endpoint in each study was the change from baseline in HbA(1C) at 12 weeks (Protocol 1) or 16 weeks (Protocol 2). RESULTS: Metformin XR reduced HbA(1C) in Protocol 1, with mean treatment differences for 1000 mg once daily vs. placebo of -0.7% at 12 weeks and -0.8% at 24 weeks (p < 0.001 for each). In Protocol 2, a clear dose-response relationship was evident at doses up to 1500 mg, with treatment differences vs. placebo of -0.6% (500 mg once daily), -0.7% (1000 mg once daily), -1.0% (1500 mg once daily) and -1.0% (2000 mg once daily). The efficacy of metformin XR 2000 mg once daily and 1000 mg twice daily were similar (mean treatment differences vs. placebo in HbA(1C) were -1.0% and -1.2%, respectively). More patients achieved HbA(1C) < 7.0% with metformin XR vs. placebo in Protocol 1 (29% vs. 14% at 12 weeks) and with once-daily metformin XR in Protocol 2 (up to 36% vs. 10% at 16 weeks). No significant changes in fasting insulin or body weight occurred. Total and low-density lipoprotein (LDL)-cholesterol improved (p < 0.05-p < 0.001) in metformin XR groups in Protocol 2. Metformin XR was well tolerated; gastrointestinal side effects were more common with metformin XR vs. placebo, but few patients withdrew for this reason (1.3% vs. 1.3% in Protocol 1 and 1.6% vs. 0.9% in Protocol 2). CONCLUSIONS: Once-daily metformin XR presents an effective and well-tolerated therapeutic option for delivering metformin in a convenient manner, which supports good compliance with therapy.
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In summary, metformin produces a highly significant reduction in body weight and waist circumference with minimal safety issues and limited issues of tolerability.
“In summary, metformin produces a highly significant reduction in body weight and waist circumference with minimal safety issues and limited issues of tolerability (22).”
From Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study (2012) · cites this paper as [22]
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- Authors
- Fujioka, K., Brazg, R. L., Raz, I., Bruce, S., Joyal, S., Swanink, R., & Pans, M.
- Affiliations
- Scripps Clinic (US)
- University of Washington (US)
- Hadassah Medical Center (IL)
- Bristol-Myers Squibb (United States) (US)
- Bristol-Myers Squibb (Belgium) (BE)
- Corresponding author
- Fujioka, K.
- ORCID
- Venue
- Diabetes Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2004-11-10
- Volume
- 7
- Issue
- 1
- Pages
- 28-39
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2095948962
- Cited by
- 73
- References
- 20
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 7 · 2020: 8 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 2 · 2014: 2 · 2013: 1 · 2012: 5
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, inadequate glycaemic control, HbA1c, dose-response relationship, once-daily dosing, sustained-release formulation, antidiabetic efficacy, drug safety, adverse events, diet and exercise, glycemic control, HbA1c variability
- MeSH terms
- Adult, Aged, Blood Glucose, Delayed-Action Preparations, Diabetes Mellitus, Type 2, Diarrhea, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Cholesterol, LDL, Male, Metformin, Middle Aged, Nausea, Time Factors, Vomiting
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